The project submitted is a collaborative effort between Neurosurgery and the Division of Endocrinology to investigate the role of vasopressin in pathology of patients with intracranial disease. Preliminary studies in patients with subarachnoid hemorrhage in whom hyponatremia occurs have indicated that the patients have contracted blood volumes. Elevated vasopressin in this situation may be secondary to a primary natriuresis and contracted volume. The problem will be investigated in consecutive patients with subarachnoid hemorrhage in whom balance studies of salt, water and daily electrolytes and hormome determinations will be made. In addition, closely controlled studies will be performed in a primate animal model in which subarachnoid hemorrhage is produced in the monkey. In preliminary studies in four monkeys, an experimental subarachnoid hemorrhage was produced by a transorbital approach. The monkeys were maintained in a chair with constant sodium intake. A prompt natriuresis after hemorrhage occurred in all animals and a fall in serum sodium from 138 to 124.6 mEq/L. There were no elevated levels of vasopressin and n volume expansion to indicate SIADH. Rather, there was correlation between the levels of oxytocin and the degree of natriuresis. Primary natriuresis may be the cause of hyponatremia after subarachnoid hemorrhage and oxytocin and the oxytocin-neurophysin may provide markers for this disorder. We propose to complete the studies of the syndrome in the monkey model and to determine the efferent limb of the natriuresis. The possible efferent limbs are hemodynamic, neural, and hormonal. We postulate that a circulating effector is responsible for the natriuresis. The circulating effortor may be oxytocin or oxytocin-neurophysin or may originate within the oxytocinergic neurons of the neurohypophysis. Extracts of urine and plasma from the monkeys will be tested for natriuretic activity by bioassay. If natriuretic activity is found (and when an appropriate natriuretic bioassay is designed), human posterior pituitary will be extracted to identify the natriuretic substance. The identity of any substance from the posterior pituitary will be compared with the material from the plasma and/or urine.